Formamide → 4-Methyl-1,3-oxazole-5-carboxylic acid

HRID 249992

Reaction equation

HRID 249992 reaction equation
C([O:3][C:4](=[O:10])[CH:5](Cl)[C:6]([CH3:8])=O)C.[CH:11]([NH2:13])=[O:12].[OH-].[Na+]>CCOC(C)=O>[CH3:8][C:6]1[N:13]=[CH:11][O:12][C:5]=1[C:4]([OH:3])=[O:10]

Participants

5

Reactant 3

HCID 713FormamideHCID 11858Ethyl 2-chloroacetoacetateHCID 14798Sodium Hydroxide

Product 1

HCID 2923114-Methyl-1,3-oxazole-5-carboxylic acidYield 64.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
120 °C

Procedure

Ethyl-2-chloroacetoacetate (1 wt; 1 eq., 1000 g) was aged with formamide (0.68 vol; ca. 2.8 eq.) and the resulting solution was heated to 120° C. After 5 hours the mixture was allowed to cool to room temperature and allowed to age under nitrogen over night. The mixture was treated with NaOH (3 M, 6 vol, reaction moderately exothermic) and stirred at room temperature for 4 hours. Ethyl acetate (6 vol) was added and the phases allowed to separate. The organic layer was discarded while the aqueous was acidified with conc. (32%) aqueous HCl to pH 2 (ca. 2.0 vol). A precipitate started to form. The suspension was treated with AcOEt (8 vol) and vigorously stirred until the bulk of the precipitate had dissolved. The aqueous phase was further extracted with AcOEt twice (6 vol each) and the combined organic layers distilled to low volume (again a suspension was observed at low volume). Fresh AcOEt (8 vol) was added and the mixture evaporated to dryness. The collected solid was placed in the oven at 40° C. over night under reduced pressure to give 4-methyl-1,3-oxazole-5-carboxylic acid (498 g, 64.5%).

Workup

  1. temperatureto cool to room temperature
  2. waitallowed to age under nitrogen over night
  3. custom3 M, 6 vol, reaction moderately exothermic) and
  4. customto separate
  5. customto form
  6. stirringvigorously stirred until the bulk of the precipitate
  7. dissolutionhad dissolved
  8. extractionThe aqueous phase was further extracted with AcOEt twice (6 vol each) and the combined organic layers
  9. distillationdistilled to low volume (again a suspension
  10. additionFresh AcOEt (8 vol) was added
  11. customthe mixture evaporated to dryness
  12. waitThe collected solid was placed in the oven at 40° C. over night under reduced pressure

Sources & evidence

ORD record
ord-01dad1690b0744549eaec54f39211a0f
Source dataset
uspto-grants-2011_01
Patent number
US07863299B2

Linked notes

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